AIMS: The aim of this study was to investigate in patients with stable angina the effects on costs of frontline diagnostics by exercise-stress testing (ex-test) vs. coronary computed tomography angiography (CTA). METHODS AND RESULTS: In two coronary units at Lillebaelt Hospital, Denmark, 498 patients were identified in whom either ex-test (n = 247) or CTA (n = 251) were applied as the frontline diagnostic strategy in symptomatic patients with a low-intermediate pre-test probability of coronary artery disease (CAD). During 12 months of follow-up, death, myocardial infarction and costs associated with downstream diagnostic utilization (DTU), treatment, ambulatory visits, and hospitalizations were registered. There was no difference between cohorts in demographic characteristics or the pre-test probability of significant CAD. The mean (SD) age was 56 (11) years; 52% were men; and 96% were at low-intermediate pre-test probability of CAD. All serious cardiac events (n = 3) during follow-up occurred in patients with a negative ex-test result. Mean costs per patient associated with DTU, ambulatory visits, and cardiovascular medication were significantly higher in the ex-test than in the CTA group. The mean (SD) total costs per patient at the end of thefollow-up were 14% lower in the CTA group than in the ex-test group, € 1510 (3474) vs. €1777 (3746) (P = 0.03). CONCLUSION: Diagnostic assessment of symptomatic patients with a low-intermediate probability of CAD by CTA incurred lower costs when compared with the ex-test. These findings need confirmation in future prospective trials.